Bottom Line:
No effects on the rate of adult neurogenesis were found.Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions.Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers.

Affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands. c.a.oomen@uva.nl

ABSTRACT

Rationale: Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown.

Objective: We examined the effects of maternal absence on structure and function of the hippocampus in female offspring.

Methods: We studied whether 24 h of maternal deprivation (MD) on postnatal day 3 altered adult neurogenesis, individual neuronal morphology and dentate gyrus (DG) structure in young adult female rats. In addition, functional alterations were addressed by studying synaptic plasticity in vitro, and spatial as well as emotional learning was tested.

Results: Adult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their dendritic arrangement. No effects on the rate of adult neurogenesis were found. Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions. In addition, spatial learning and contextual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala-dependent fear memory.

Conclusion: Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers. This may be relevant for the reduced hippocampal volume observed in depression and the increased vulnerability of women to develop depression.

Fig4: Effects of MD on fear conditioning. a MD does not affect the amount of freezing behaviour in response to the context (p = 0.35). b During cued fear conditioning, MD animals (n = 10) show increased freezing in response to the novel environment (p = 0.002) and an increased freezing behaviour in response to the tone when compared to controls (both groups, n = 10, p < 0.05)

Mentions:
Fear conditioning did not reveal any effects of MD on baseline freezing behaviour nor on freezing behaviour during training (data not shown), supporting the notion that MD does not affect overall anxiety in female rats later in life. Twenty-four hours later—during the contextual test—both groups showed comparable freezing behaviour (F1,35 = 0.92, p = 0.35; Fig. 4a). While contextual fear conditioning was not affected by MD, exposure to a novel environment 24 h after the cue-shock training did result in elevated levels of freezing in MD compared to CON animals (p = 0.002; Fig. 4b). Subsequent exposure to the earlier cue in this novel environment caused extensive freezing behaviour, which also differed significantly between MD and CON animals (p < 0.05; Fig. 4b).Fig. 4

Bottom Line:
No effects on the rate of adult neurogenesis were found.Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions.Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers.

Affiliation:
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands. c.a.oomen@uva.nl

ABSTRACT

Rationale: Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown.

Objective: We examined the effects of maternal absence on structure and function of the hippocampus in female offspring.

Methods: We studied whether 24 h of maternal deprivation (MD) on postnatal day 3 altered adult neurogenesis, individual neuronal morphology and dentate gyrus (DG) structure in young adult female rats. In addition, functional alterations were addressed by studying synaptic plasticity in vitro, and spatial as well as emotional learning was tested.

Results: Adult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their dendritic arrangement. No effects on the rate of adult neurogenesis were found. Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions. In addition, spatial learning and contextual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala-dependent fear memory.

Conclusion: Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers. This may be relevant for the reduced hippocampal volume observed in depression and the increased vulnerability of women to develop depression.